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Human IVIG treatment in a neurological disease model for Enterovirus A71 infection in 28-day-old AG129 mice
Christopher J Peterson1, Brett L Hurst2, W Joseph Evans2
1Institute for Antiviral Research, Department of Animal, Dairy, and Veterinary Sciences, 5600 Old Main Hill, Utah State University, Logan, UT, 84322, USA; Department of Animal, Dairy, and Veterinary Sciences, Utah State University, 5600 Old Main Hill, Logan, UT, 84322, USA; Carilion Clinic-Virginia Tech Carilion School of Medicine, 2 Riverside Circle, Roanoke, VA, 24016, USA.
Abstract:
Enterovirus A71 can cause serious neurological disease in young children. Animal models for EV-A71 are needed to evaluate potential antiviral therapies. Existing models have limitations, including lack of lethality or crucial disease signs. Here we report the development of an EV-A71 model in 28-day-old mice. Virus was serially passaged until it produced consistent lethality and rear-limb paralysis. Onset of disease occurred between days 6-9 post-infection, with mortality following weight loss and neurological signs on days 9-14. In addition, a single administration of human intravenous immunoglobulin at doses of 200, 400 and 800 mg/kg at 4h post-infection was evaluated in the model. Protection from weight loss, neurological signs, and mortality (between 50 and 89%) were observed at doses of 400 mg/kg or greater. Based on these results, IVIG was selected for use as a positive control in this acute model, and suggest that IVIG is a potential therapeutic for EV-A71 infections.
Insights
A new mouse model for Enterovirus A71 (EV-A71) infection in young mice shows lethality and paralysis. Human intravenous immunoglobulin (IVIG) demonstrated significant protection, suggesting its therapeutic potential for EV-A71.
Area of Science:
- Virology
- Neurology
- Infectious Diseases
Background:
- Enterovirus A71 (EV-A71) causes severe neurological illness in children.
- Existing animal models for EV-A71 lack critical disease manifestations and lethality.
- Effective antiviral therapies require robust and relevant preclinical models.
Purpose of the Study:
- To develop a lethal mouse model for EV-A71 infection.
- To evaluate the therapeutic efficacy of human intravenous immunoglobulin (IVIG) in the developed model.
Main Methods:
- Serial mouse brain passage of EV-A71 to establish a lethal strain.
- Infection of 28-day-old mice with the adapted EV-A71 strain.
- Administration of varying doses of IVIG post-infection to assess therapeutic effects.
Main Results:
- The adapted EV-A71 strain caused consistent lethality and hind limb paralysis in mice.
- Disease onset occurred 6-9 days post-infection, with mortality between 9-14 days.
- IVIG treatment (≥400 mg/kg) significantly reduced weight loss, neurological signs, and mortality (50-89% protection).
Conclusions:
- A novel, lethal mouse model for EV-A71 infection was successfully developed.
- Human IVIG shows significant therapeutic potential against EV-A71, warranting further investigation.
- This model serves as a valuable tool for evaluating EV-A71 therapeutics.
